PROLONGATION OF CANINE INTESTINAL ALLOGRAFT SURVIVAL WITH RS-61443, CYCLOSPORINE, AND PREDNISONE

The efficacy of RS-61443 and cyclosporine utilized either alone or in combination was assessed in both a segmental heterotopic and total ort hotopic canine intestinal transplant model. Twenty-eight dogs underwen t segmental (150-cm) heterotopic intestinal transplants and five dogs total orthotopic transplants. Five heterotopic groups were compared: g roup 1, no immunosuppression; group 2, cyclosporine and prednisone; gr oup 3, RS-61443, cyclosporine and prednisone; group 4, RS-61443 and pr ednisone; and group 5, RS-61443 and subtherapeutic cyclosporine. Group 3 animals achieved a median survival of 136 days, while the median su rvivals of groups 1, 2, 4, and 5 were less-than-or-equal-to 10 days (P < .001). Twenty deaths in groups 1 through 5 were secondary to allogr aft rejection, two were due to infection, and two were unexplained. Fo ur animals in group 3 were sacrificed, one at 83 days due to diarrhea and weight loss and three at the termination of the study. The median survival of five dogs undergoing total orthotopic transplantation (gro up 6) was 27.0 days and was significantly longer than groups 1, 4, and 5 (P < .01). No dog in this group had intestinal rejection-however, f our were sacrificed due to weight loss and one died of malnutrition. T he combination of RS-61443 and cyclosporine significantly prolonged in testinal allograft survival in both the heterotopic and orthotopic tra nsplant models. Clinically, this combination may be promising for both combined liver-intestinal and isolated intestinal transplantation.